DESCRIPTION: (Scanned from the applicant's abstract) The suppression of menstrual cyclicity due to strenuous exercise can cause infertility, severe bone demineralization, increase fracture risk, and possibly increase the risk of cardiovascular disease. Recent findings in humans and animals have strongly suggested that exercise-induced menstrual disturbances are primarily caused by low energy availability and not by other factors, such as the physical stress of exercise per se. While some studies have quantified energy balance associated with short-term decreases in plasma levels of reproductive hormones, the bioenergetics associated with the induction and reversal of clinically recognized menstrual disturbances in exercising women remain unclear. The first specific aim of this proposal is to test the hypothesis that there is a direct relationship between the severity of exercise-induced menstrual disturbances and the magnitude of negative energy balance. In addition to weight loss, crosssectional studies in humans suggest that exercise-induced menstrual disturbances are associated with adaptive mechanisms to conserve energy, i.e., alterations in circulating metabolic hormones and substrates, and reductions in components of 24 h energy expenditure such as metabolic rate. Since in vivo and in vitro studies using animal models have suggested mechanistic roles for key metabolic hormones and substrates in the modulation of GnRH neuronal activity with changes in energy balance, prospective studies in humans are now necessary to identify the time course and magnitudes of change of potential key metabolic signals during the development of EIMD. The second specific aim of this proposal is to test the hypothesis that exercise-induced menstrual disturbances are triggered by the development of a particular metabolic state defined by adaptive mechanisms to conserve energy. The significance of this research relates to conditions of infertility, delayed puberty, anovulation, anorexia nervosa, exercise-induced amenorrhea, and the recently identified high incidence of luteal phase disturbances and anovulatory cycles in women exercising even at recreational levels. We expect the results of these studies to provide new and useful information for making specific recommendations regarding the exercise and dietary practices concomitant with maintaining normal, ovulatory menstrual cycles and adequate levels of circulating estrogen and progesterone. The results will also expand our understanding of the mechanism of the modulation of reproductive function by energy availability.